Mesenchymal Stem Cells as Anti-Inflammatory Agents in Chronic Kidney Disease: A Systematic Review and Meta-Analysis
Lukman Pura1,2, Raeni Dwi Putri3, Muh Arya Prahmana3
1Doctoral Study Program of Medical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40132, Indonesia.
Background:
Chronic kidney disease (CKD) is largely driven by inflammation. Mesenchymal stem cells (MSCs) show therapeutic potential; however, their efficacy across CKD etiologies remains unclear.
Methods:
Comprehensive searches were conducted in PubMed, Cochrane, ScienceDirect, Scopus and Google Scholar. Effect sizes for inflammation and renal function outcomes were meta-analyzed.
Results:
Of 2514 studies screened, 52 met inclusion criteria (49 animal studies, 3 randomized controlled trials). In animal models, MSCs significantly reduced interleukin-6 (mean difference [MD] = -155.80; 95% CI: -249.10, -62.51; p = 0.001) and tumor necrosis factor-α (TNF-α) (MD = -35.53; 95% CI: -52.75, -18.30; p < 0.0001). In patients, TNF-α reduction was not significant (MD = -0.74; 95% CI: -2.20, 0.73; p = 0.32). Serum creatinine decreased in animals (MD = -0.38; 95% CI: -0.46, -0.29; p < 0.00001), but not in patients (MD = -0.59; 95% CI: -1.92, 0.74; p = 0.39). Blood urea nitrogen decreased in animals (MD = -19.27; 95% CI: -23.50, -15.04; p < 0.00001), and glomerular filtration rate improved (standardized MD = 1.83; 95% CI: 0.51, 3.15; p = 0.007), with no change in patients.
Conclusion:
MSCs improve inflammation and renal function in CKD animal models; however, evidence in patients remains inconclusive.
Insights
Mesenchymal stem cells (MSCs) show promise for treating chronic kidney disease (CKD) by reducing inflammation and improving kidney function in animal models. However, current evidence in human patients remains inconclusive, requiring further investigation.
Area of Science:
- Nephrology
- Regenerative Medicine
- Immunology
Background:
- Chronic kidney disease (CKD) pathogenesis is significantly influenced by inflammatory processes.
- Mesenchymal stem cells (MSCs) are being investigated for their therapeutic potential in managing inflammatory conditions like CKD.
- The effectiveness of MSCs across diverse CKD etiologies requires further clarification.
Purpose of the Study:
- To systematically evaluate the efficacy of Mesenchymal stem cells (MSCs) in modulating inflammation and improving renal function in chronic kidney disease (CKD).
- To compare the effects of MSCs in preclinical (animal) models versus human clinical trials for CKD.
- To synthesize existing evidence through meta-analysis to determine the current therapeutic standing of MSCs for CKD.
Main Methods:
- A comprehensive literature search was performed across major scientific databases including PubMed, Cochrane, ScienceDirect, Scopus, and Google Scholar.
- Studies involving Mesenchymal stem cells (MSCs) for chronic kidney disease (CKD) were screened for inclusion criteria.
- Effect sizes for key inflammation markers (e.g., TNF-α, IL-6) and renal function parameters (e.g., serum creatinine, BUN, GFR) were meta-analyzed.
Main Results:
- In animal models of CKD, Mesenchymal stem cells (MSCs) significantly reduced key inflammatory markers like interleukin-6 and tumor necrosis factor-α.
- MSCs treatment led to significant improvements in renal function markers, including decreased serum creatinine and blood urea nitrogen, and improved glomerular filtration rate in animal studies.
- In the limited human trials (3 RCTs), Mesenchymal stem cells (MSCs) did not show statistically significant reductions in tumor necrosis factor-α or significant improvements in serum creatinine and glomerular filtration rate.
Conclusions:
- Mesenchymal stem cells (MSCs) demonstrate significant therapeutic benefits in reducing inflammation and improving renal function within animal models of chronic kidney disease (CKD).
- The current clinical evidence from human trials is insufficient to confirm the efficacy of Mesenchymal stem cells (MSCs) for treating chronic kidney disease (CKD) in patients.
- Further robust clinical trials are necessary to ascertain the true therapeutic value of Mesenchymal stem cells (MSCs) for human chronic kidney disease (CKD) patients.
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